Role of the Ubiquitin-Proteasome System in Mammalian Male Germ Cell Differentiation and Reproductive Fitness

The ubiquitin-proteasome system (UPS) is fundamental for the development and differentiation of male mammalian germ cells. As a key pathway for protein degradation, the UPS maintains cellular homeostasis by removing misfolded, damaged, or excess proteins, thus enabling cells to adapt to physiological and environmental changes. In male reproduction, the UPS regulates critical processes from spermatogenesis to the functionality of mature spermatozoa. During spermatogenesis in seminiferous tubules, the UPS orchestrates cell cycle regulation, apoptosis, and chromatin remodeling, ensuring that only the most viable germ cells differentiate. In the epididymis, the UPS facilitates sperm maturation, granting motility and functional characteristics. In addition, the UPS is essential for sperm capacitation in the female reproductive tract, which is a process critical for fertilization. Dysregulation of the UPS can severely impair male fertility and contribute to infertility and other reproductive disorders. This review provides a detailed examination of the role of the UPS in spermatogenesis, sperm maturation in the epididymis, and capacitation in the female reproductive tract. By exploring the molecular mechanisms underlying these processes, we highlight the clinical implications of UPS dysfunction and offer a comprehensive understanding of its contribution to mammalian reproductive success.